Cathepsin B is activated as an executive protease in fetal rat alveolar type II cells exposed to hyperoxia

Lee, Hyeon Soo; Kim, Chun Ki

doi:10.3858/emm.2011.43.4.027

Cited by 9 publications

(17 citation statements)

References 33 publications

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“…It has been reported that CD147 was increased in bronchoalveolar lavage fluid obtained from COPD patients, which may suggest its modulatory role in MMP9 activation 10 . Previously published studies indicate that cathepsin B mediates human alveolar epithelial cell death stimulated by lipopolysaccharides 36 and executing fetal ATII cell death induced by ROS generated by hyperoxia 37 . Our results suggest that cathepsin B may contribute to ATII cell injury under high oxidative stress induced by CS and in emphysema as well.…”

Section: Discussionmentioning

confidence: 99%

The cytoprotective role of DJ-1 and p45 NFE2 against human primary alveolar type II cell injury and emphysema

Tan

Bahmed

Lin

et al. 2018

Sci Rep

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Emphysema is characterized by irreversibly enlarged airspaces and destruction of alveolar walls. One of the factors contributing to this disease pathogenesis is an elevation in extracellular matrix (ECM) degradation in the lung. Alveolar type II (ATII) cells produce and secrete pulmonary surfactants and proliferate to restore the epithelium after damage. We isolated ATII cells from control non-smokers, smokers and patients with emphysema to determine the role of NFE2 (nuclear factor, erythroid-derived 2). NFE2 is a heterodimer composed of two subunits, a 45 kDa (p45 NFE2) and 18 kDa (p18 NFE2) polypeptides. Low expression of p45 NFE2 in patients with emphysema correlated with a high ECM degradation. Moreover, we found that NFE2 knockdown increased cell death induced by cigarette smoke extract. We also studied the cross talk between p45 NFE2 and DJ-1. DJ-1 protein is a redox-sensitive chaperone that protects cells from oxidative stress. We detected that cigarette smoke significantly increased p45 NFE2 levels in DJ-1 KO mice compared to wild-type mice. Our results indicate that p45 NFE2 expression is induced by exposure to cigarette smoke, has a cytoprotective activity against cell injury, and its downregulation in human primary ATII cells may contribute to emphysema pathogenesis.

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Section: Discussionmentioning

confidence: 99%

The cytoprotective role of DJ-1 and p45 NFE2 against human primary alveolar type II cell injury and emphysema

Tan

Bahmed

Lin

et al. 2018

Sci Rep

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“…Animal care and experimental procedures were carried out in accordance with the Guidelines for Animal Experimentation of Kangwon National University School of Medicine with the approval of the Institutional Animal Care. After extraction of fetal lungs and isolation of fetal type II cells as described previously,12,13,15,16 type II epithelial cells were harvested with 0.25% (wt/vol) trypsin in 0.4 mM EDTA and plated at a density of 10×10 5 cells/well on 6-well plates precoated with fibronectin (4 µg/well). Plates containing cells were incubated for an additional 24 h in serum-free DMEM and then incubated in a culture chamber with ProOx Oxygen Controller with Low profile right angle sensor (BioSpherix, Redfield, NY, USA).…”

Section: Methodsmentioning

confidence: 99%

“…For the study of preincubation of rIL-10, the cultured type II cells were treated with rIL-10 (R&D Systems, Minneapolis, MN, USA), at a concentration of 250 ng/mL,13 for 1 h before hyperoxia exposure. And for inhibition studies, the cells in an identical manner were preincubated with specific inhibitor of cathepsin B, CA074Me (Calbiochem, San Diego, CA, USA), at a concentration of 100 µM3,12 for 1 h prior to 65%-hyperoxia. The concentrations of 250 ng/mL of rIL-1013 and 100 µM cathepsin B-inhibitor3,12 were chosen based on previous studies, which showed that these concentrations greatly reduced cell death in fetal alveolar type II cells 12,13…”

Section: Methodsmentioning

confidence: 99%

“…We have previously shown that fetal alveolar type II cell death is largely mediated by necrosis during the acute stage of 65%-hyperoxia, and fetal alveolar type II cell necrosis is mediated by cathepsin B, but not caspase-3, during the acute stage of 65%-hyperoxia 12. Also we have previously defined that an imbalance between the pro-inflammatory cytokine, IL-8 and the anti-inflammatory cytokine, IL-10 is generated in fetal alveolar type II cells exposed to 65%-hyperoxia, and that preincubation of fetal alveolar type II cells with recombinant IL-10 (rIL-10) prior to hyperoxia reduces cell necrosis and release of IL-8 in these cells during hyperoxia 13…”

Section: Introductionmentioning

confidence: 98%

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Interleukin-10 Down-Regulates Cathepsin B Expression in Fetal Rat Alveolar Type II Cells Exposed to Hyperoxia

Lee

Kim

2013

Yonsei Med J

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PurposeHyperoxia has the chief biological effect of cell death. We have previously reported that cathepsin B (CB) is related to fetal alveolar type II cell (FATIIC) death and pretreatment of recombinant IL-10 (rIL-10) attenuates type II cell death during 65%-hyperoixa. In this study, we investigated what kinds of changes of CB expression are induced in FATIICs at different concentrations of hyperoxia (65%- and 85%-hyperoxia) and whether pretreatment with rIL-10 reduces the expression of CB in FATIICs during hyperoxia.Materials and MethodsIsolated embryonic day 19 fetal rat alveolar type II cells were cultured and exposed to 65%- and 85%-hyperoxia for 12 h and 24 h. Cells in room air were used as controls. Cytotoxicity was assessed by lactate dehydrogenase (LDH) released into the supernatant. Expression of CB was analyzed by fluorescence-based assay upon cell lysis and western blotting, and LDH-release was re-analyzed after preincubation of cathepsin B-inhibitor (CBI). IL-10 production was analyzed by ELISA, and LDH-release was re-assessed after preincubation with rIL-10 and CB expression was re-analyzed by western blotting and real-time PCR.ResultsLDH-release and CB expression in FATIICs were enhanced significantly in an oxygen-concentration-dependent manner during hyperoxia, whereas caspase-3 was not activated. Preincubation of FATIICs with CBI significantly reduced LDH-release during hyperoxia. IL-10-release decreased in an oxygen-concentration-dependent fashion, and preincubation of the cells with rIL-10 significantly reduced cellular necrosis and expression of CB in FATIICs which were exposed to 65%- and 85%-hyperoxia.ConclusionOur study suggests that CB is enhanced in an oxygen-concentration-dependent manner, and IL-10 has an inhibitory effect on CB expression in FATIICs during hyperoxia.

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“…HALI ( 2 ), ARDS ( 3 ), chronic obstructive pulmonary diseases ( 4 ), pulmonary fibrosis ( 5 ) and other lung diseases caused by oxidative stress, are the primary reasons for type II alveolar epithelial cell (AEC-II) apoptosis. AEC-II are the primary targeting cells for high oxygen ( 2 , 6 ), AEC-II apoptosis is considered to be the underlying pathogenesis of HALI ( 7 – 9 ), and the inhibition of AEC-II can effectively reduce the degree of HALI apoptosis ( 10 , 11 ). The survival or apoptosis of AEC-II directly affect the degree of lung injury and repair ( 12 ).…”

Section: Introductionmentioning

confidence: 99%

miR‑21‑5p regulates type II alveolar epithelial cell apoptosis in hyperoxic acute lung injury

et al. 2018

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Hyperoxia-induced acute lung injury (HALI) as one of the most common complications in patents on mechanical ventilation, and there are no efficient methods to overcome this at present. It was hypothesized that microRNA 21-5p(miR-21-5p) can promote the survival of type II alveolar epithelial cells (AECII), alleviating HALI. The present study aimed to combine gene chip analysis with the overexpression miR-21-5p to develop a novel therapeutic option for HALI. It was found that AECII apoptosis was an important pathogenic event in the development of HALI, and the overexpression of miR-21-5p prevented HALI, associated with reducing AECII apoptosis. These results were obtained using adenoviral/lentiviral vectors, which overexpressed miR-21-5p, to transfect AECII cells in vitro and in vivo. It was found that the overexpression of miR-21-5p reduced the apoptotic rate of the AECII cells. In addition, miR-21-5p decreased the ratio of B-cell lymphoma 2 (Bcl-2)-associated X protein/Bcl-2 and the expression of caspase-3. It was also revealed that the overexpression of miR-21-5p alleviated acute lung injury in adult rats exposed to a hyperoxic environment. These results suggest that miR-21-5p may become a novel therapeutic option for patients with HALI, by protecting AECII cells from apoptosis.

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Cathepsin B is activated as an executive protease in fetal rat alveolar type II cells exposed to hyperoxia

Cited by 9 publications

References 33 publications

The cytoprotective role of DJ-1 and p45 NFE2 against human primary alveolar type II cell injury and emphysema

The cytoprotective role of DJ-1 and p45 NFE2 against human primary alveolar type II cell injury and emphysema

Interleukin-10 Down-Regulates Cathepsin B Expression in Fetal Rat Alveolar Type II Cells Exposed to Hyperoxia

miR‑21‑5p regulates type II alveolar epithelial cell apoptosis in hyperoxic acute lung injury

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